Hollow fiber filters whose walls may be porous and semipermeable possess excellent filtration performance and properties that are applicable in many fields and applications. Hollow fibers (HFs) are used extensively in water purification, separation of constituents from biological fluids, dialysis, reverse osmosis, gas separation, cell culture devices, as well as many others. In spite the variety of uses, hollow fiber based filtration devices have a common structure and mode of operation. The filtration unit is the hollow fiber module (HFM), and while the HFM structure may vary somewhat from one application to another, it nevertheless possesses a generally common structure and method of assembly.
Typically, individual hollow fibers are combined into a “bundle” (also referred to as “clusters”) in which fibers may be optionally retained by a sleeve of some kind, typically a net sleeve. The bundle is then further placed in a protective housing or shell which is, typically, tubular in nature. The hollow fibers within the shell, typically, extend about the length of the shell in a manner that disposes the fibers to potting with a polymeric or other material at each end of the shell. The hollow fibers can thus be embedded in the polymeric material upon its polymerization and solidification. In the same process, the solidified potting material, which may be of any thickness, but typically 5-10% the length of the shell, forms a solid end cap, potted cap or “wall” at each end of the shell. The construction results in formation of a chamber between the inner walls of the shell and the outer walls of the hollow fibers, and between the potted end caps.
As the hollow fiber ends may clog during the potting process, known methods are applied either to protect the ends of the hollow fibers from clogging during potting or to open such ends after potting. A continuous flow path is therefore retained through the entire length of the hollow fibers, including through the polymeric potting material. The objective being not only to maintain a continuous flow path through the entire length of the hollow fibers, but also to form a chamber, a permeate chamber, within the shell for storing or collecting fluids emanating from the fiber walls; such an assembly is known as a Hollow Fiber Cartridge (HFC).
Typically, adapters are added to the ends of the shell or HFC which direct the fluid to be filtered or retentate into the hollow fibers at one end and to direct such fluid exiting the hollow fibers at the other end of the HFC. Additional adapters may be added to the shell to provide a conduit from the permeate chamber for collecting such permeate.
Apparent from the generalized structure, having both an inlet and outlet to flow the retentate and a means for collecting filtered material is that the HFM provides an efficient unit of filtration. In the HFM, retentate is directed into the semipermeable HFs, generating a linear flow through the fibers. A higher pressure within the fibers relative to the filtrate chamber generates a second flow, through HF porous walls, perpendicular to the first fluid or retentate flow direction. The fluid fraction traversing the membrane may be fractionated or filtered based on membrane properties, such as, membrane pore size; particles larger than the pores are retained by the membrane and particles smaller than the pores pass through the membrane into the permeate chamber. Such a filtration process is known as cross flow filtration, or tangential flow filtration, which is used extensively and is generally well understood. Liquid filtered through the HF membrane can therefore be collected in the permeate chamber where it may be harvested.
The HFC lacks the adapters for directing retentate inflow and outflow to and from the hollow fibers. However, the cartridge shell wall can be rendered permeable to the unrestricted flow of permeate. Furthermore, the cartridge may be converted to an HFM by its insertion into a separate, module housing which contains such adapters for directing retentate inflow and outflow. It is obvious, however, that when creating such an HFM, a partition is required between the retentate chamber (the collective inner lumens of the fibers) and the permeate (or filtrate) chamber, which separation is readily accomplished with gaskets, “O” rings, or other well-known means, circumscribing the ends of the cartridge and sealing the gap between those ends and the module housing. Additionally, the module housing also contains a harvest port for collecting filtrate emerging from the hollow fibers; pores in the HFC shell provide the means for such filtrate to flow across the cartridge shell wall to the harvest ports for harvest. Because of their similarities, the term HFCM is used when referring to features contained in both HFC and HFM.
The diversity of the HFM can be greatly increased by the selection of hollow fiber material, physical configuration of the HFM, adjustment of the chemical and physical properties of the fibers, regulation of the process of filtration by controlling the flow through and across the fibers and by other manipulations.
The HFM may also provide an excellent platform for scale up. By increasing the number of fibers in the HFC, a volumetric scale up can be achieved. Large filters with densely packed fibers may provide significant benefits, including an obvious increase in membrane surface area, where the increase is to the third power of the radius of the HFC. In comparison, only a linear increase in surface area is achieved by simply adding more HFM to a manifold of such modules. Additionally, one large filter can greatly reduce the foot print of the filtration system, eliminating some of the complexity of a filter manifold. The complexity of the manifold with its interconnecting tubing, pipes, valves, and monitoring instruments, greatly complicates cleaning, sterilization, and validation of a process using such a complex system. These are critical issues in certain industries, including the pharmaceutical, food, chemical, water, sewage treatment, etc. Furthermore, when scaling up a process, transitioning from a smaller scale process containing a single HFM to a larger scale system containing multiple modules may complicate a critical process.
Large scale filters are desirable in many fields primarily for processing large volumes of fluids, for filtering complex mixtures and for increasing rates of filtration. Yet, in spite of the need and benefits for large HFMs, such modules are not readily available. Technical construction limits of such large filters may be involved. While typical construction methods result in reliable “small to moderate” scale HFM, <10 m2 (for a 60 cm long fiber, and 1 mm ID), they become unreliable and costly when applied to production of large filters, where large scale may be >10 m2 (for a 60 cm long fiber, and 1 mm ID). More specifically, the complications increase for a HFM (with the same parameters) with membrane surface area >20 m2, and increase even more with even larger filters. It would be desirable therefore to develop a process for constructing a large HFM that would eliminate or minimize the problems observed by current HFM construction methods. While it is possible to increase surface area with narrower and/or longer fibers, those options may not be desirable in many applications. Some factors associated with the limits to forming large filters, include:
Potting Material—
The potting material used to embed the HFs at each end of the HFC is a common source of potential problems which can become more severe as the diameter of the HFC increases. For example, potting materials, including epoxies and polyurethane, shrink somewhat after curing. The degree of shrinkage will depend greatly on the material, including its exposure and reaction to heat, moisture, chemicals, radiation, etc; where such shrinkage or change in shape may be very small and insignificant when constructing a small diameter HFM; but, it becomes very significant with increased diameter of the potted area; noting that total shrinkage is a function of the material shrinkage coefficient times length or diameter of the pot. One can appreciate that such shrinkage can affect overall diameter of the pot. It can cause structural failures such as cracking in the pot and/or forcing the pot to shrink inward, towards the center of a rounded potted area or along stress boundaries. This is particularly observed when a potting agent and the shell end cap of the HFC are different materials, each having different expansion and shrinkage properties (i.e. coefficients of thermal expansion) (preferably the shell end cap and the shell have identical coefficients of thermal expansion). For example, in the case where the shell end cap is polysulfone and the potting material is epoxy, the bond between the polysulfone and epoxy may be affected differently by heat treatment, as is the case when heat sterilizing the HFCM in an autoclave. What is frequently noted is that the epoxy, with greater shrinkage than polysulfone, will pull away from the polysulfone to form a passageway between the filtrate chamber and the retentate chamber, compromising the integrity of the HFCM and rendering the HFCM useless. This is observed on occasion in a HFCM of about 4″ in diameter and is more frequently observed in a 6″ diameter HFCM.
Similarly, when dealing with two different materials with different coefficients of expansion, it becomes problematic to form a secure bond between the two materials, particularly following exposure to heat. Both materials will expand and contract differently, stressing the bond in between them. Selection of materials with similar coefficients of expansion and using techniques to enhance the bond between the two materials may be used to support the stability of the bond; nevertheless, this becomes more difficult to control with increased diameter of the HFC. Thus, it would be desirable to form an HFC or HFM where such incompatibility between different materials of construction is minimized or eliminated.
Packing Density—
The packing methods of individual fibers or fiber bundles within the HFC can have a great effect on the number of fibers that may be packed in a given volume. The packing method may also have a profound effect on filtration efficiency and on the uniformity of filtrate formation. A tight, randomly packed bundle may result in a higher filtration rate per fiber on the periphery of the bundle, than from fibers in the internal confines of the bundle, particularly in a tight pack, where there may be significant resistance to filtrate flow by the intervening fibers. In a large HFM or HFC, such restrictions may result in reduced effective filtration rate and filtration capacity, thereby reducing the effective scale up capacity. Therefore, it would be desirable to pack individual fibers or fiber bundles in arrangement(s) that maximize fiber packing density and minimize the potential obstructions to filtrate flow. Other benefits to controlled fiber packing arrangements will be described.
Structural—
As the size of the HFM is increased, a proportional increase in stress forces acting on the module are expected. Increased stresses based on the following may be expected: Weight—The weight of the module can complicate its handling. The increased weight of the module may cause its own distortion, particularly when heated during sterilization in an autoclave. Assembly—assembly of parts, fitting, and bonding large surfaces may increase the potential for failure; again, this may be amplified by heating.
Process—
The flow rates through a large HFM can be very high and occur at high pressures. Considering the large surface area of the potted ends, it can be subjected to significant pressures, potentially causing the potted ends to collapse. Reinforcing the potted ends, as will be described, to minimize the distortive effect of pressure when building large filters, would be very beneficial.
Integrity—
The larger the HFM and the more hollow fibers packed into it, the greater the probability that a fiber may be damaged or will be damaged during handling. Loss of integrity even in a single fiber may render the entire HFM useless. A break in a hollow fiber will cause contaminating flow from the retentate stream to enter the filtrate stream. The potential loss of integrity due to such a minor defect is also an important reason discouraging construction of such large filters. Using current methods of construction, a HFM may be fully assembled before it is determined that the HFM lacks integrity, in which case the HFM must be discarded. This, in addition to the other potential hazards during construction of large HFMs by current methods, discourages construction of such filters and results in greatly increased manufacturing cost. The proposed method of the invention would minimize or eliminate many of the potential risks to construction of large HFCMs. As part of the invention, methods of hollow fiber filter assembly are described; the assembly of which is not limited to the particular HFCM exemplified.
Sanitary Construction—
As many large HFCMs may be used in the food or medical industries, an HFCM needs to comply with the requirements of these industries. Sanitary design may be one of those requirements. There should be no crevices, dead zones, or other factors in the design that trap contaminants, affect clean-ability of the module or affect sterilization of the module. For example, the use of threading would not be desirable. Threading has been shown to be very unsanitary in critical applications requiring sanitary design. Another unsanitary design feature is the presence of dead zones that are inaccessible by normal means; such stagnant zones within the HFCM, or that are associated with the HFCM, entrap contaminants and inhibit their removal. The results are decreased clean-ability, decreased ability to maintain sterility, and increased process contamination. This invention minimizes unsanitary factors and maximizes full and homogeneous penetration into all parts of the HFCM.